Interdisciplinary Ph.D. in Biomedical Sciences

Drs. Kim Tran, Eric Wauson and Sarah Clayton, Department of Physiology and Pharmacology

We are interested in various aspects of cardiovascular pathobiology and therapeutics, in particular disorders associated with atherosclerosis, menopause, hypertension, and heart failure. We use a combination of molecular, biochemical, and cellular approaches, coupled with animal studies. Current projects include:

1. Novel receptor-based therapy for atherosclerosis: (Drs. Kim Tran, Eric Wauson and Sarah Clayton) Atherosclerosis is a leading cause of cardiovascular disease. We have identified unique interactions between the G protein-coupled estrogen receptor (GPER) and critical points in the molecular regulation of cardiovascular functions. This project tests new tools developed from these interactions for the prevention of atherosclerosis.
2. Novel receptor-based modulation of cardiac catabolism: (Drs. Kim Tran and Eric Wauson) Catabolic derangement is a major cause of cardiovascular disease. This project aims to delineate the roles of GPER in the regulation of cardiac catabolic functions under normal or stressed conditions, with the goal of developing novel therapies that minimize cardiac stress.
3. Novel receptor-based management of inflammatory response: (Drs. Eric Wauson and Kim Tran) Inflammation is a major cause of cardiovascular disease. This project examines the roles of GPER in the mechanisms that regulate cellular inflammatory responses and explores targeting of GPER in the management of inflammation in the cardiovascular system.

Dr. Kim Tran, Department of Physiology and Pharmacology

Constitutive and dynamic protein-protein interactions (PPIs) are important for cardiovascular functions, and derangements in PPIs are involved in the pathogenesis of many cardiovascular disorders. We use a combination of molecular, biochemical, and cellular techniques to identify and characterize novel PPIs that are involved in the regulation of signaling via calcium in normal and altered physiological states, with a goal of exploiting them for the prevention and management of cardiovascular disease.

Dr. Maria Barnes, Department of Biochemistry and Nutrition

Greater than 75% of post-menopausal women are hypertensive. These women are more likely to have uncontrolled hypertension, suggesting that the efficacy of drug treatment or hormone replacement therapy is inconsistent in the management of their blood pressure. The overarching goal of our laboratory is to identify mechanisms that can be exploited for effective treatment of hypertension in post-menopausal women. We utilize in part in vivo (animal models) and in vitro (neuronal cell cultures) models and a variety of molecular and histological techniques to test our novel hypotheses.

Dr. Maria Barnes, Department of Biochemistry and Nutrition; Dr. Francesca Di Sole, Department of Physiology and Pharmacology, Des Moines University, and Dr. Victor Babich, Mercy College of Health Sciences

Obesity represents a major risk factor for hypertension and raises blood pressure by impairing renal salt handling and pressure natriuresis, causing volume expansion via activation of the brain-kidney axis. Dietary guidelines for obesity typically focus on caloric nutrients, while intake of noncaloric nutrients such as salt is rarely discussed. However, high intake of salt is associated not only with increased risk of hypertension but also with the development of obesity. The mechanisms of this salt effect are largely unknown. This study aims to identify mechanisms activated by the brain-kidney axis to control the effect that salt has on increasing the risk for developing hypertension in obesity and provide insights into potential interventional approach against hypertension associated with obesity.

Dr. Yujiang Fang, Department of Microbiology and Immunology

Interleukin-39 (IL-39) is the most recent member of the interleukin-12 cytokine family. It is composed of a heterodimeric chain-pairing of IL-23p19 and EBI3. IL-39 has been studied only on SLE. Its role in the development and progress of neoplasia has not been investigated yet. Prostate cancer is the most common cancer in males, and many brain tumors are lethal tumors. We previously reported that IL-39 significantly inhibited proliferation and promoted apoptosis of bladder cancer, and IL-37 was a very promising radiosensitizer for prostate cancer. The purpose of this study is to investigate 1) if IL-39 has any direct effects on proliferation, apoptosis and senescence of prostate cancer and brain tumors by using different tumor cell lines, 2) if it could act as a potential radiosensitizer for prostate cancer and brain tumors and 3) the potential molecular mechanisms. Such a study might provide new strategies for immunotherapy and help enhancement of radiation therapy for prostate cancer and brain tumors.

Drs. Vanja Duric and Francesca Di Sole, Department of Physiology and Pharmacology

Chronic stress can significantly diminish the ability of the central nervous system to regulate both neurological and systemic stress responses required to maintain normal body homeostasis. Clinical depression, anxiety and other psychiatric symptoms are commonly present in patients with different chronic systemic diseases such as chronic pain and chronic kidney disease. We are interested in studying neural mechanisms underlying stress-induced interruption of the brain’s ability to communicate with and regulate the function of peripheral organ systems, especially the brain-kidney crosstalk. Through utilization of a variety of biochemical and pharmacological approaches in combination with stress animal models, the overall goal of this interdisciplinary research is to aid the development of more effective treatment, diagnostic and prevention strategies for management of not only depression, but also of mental health comorbidities associated with different systemic illnesses such as acute kidney injury and chronic kidney disease.

Dr. Elitsa Ananieva-Stoyanova, Department of Biochemistry and Nutrition

Progress in cancer immunotherapy raised hopes that lymphoma patients will experience long-term control or eradication of the disease. However, for many patients the cancer immunotherapies have been unsuccessful due to substantial drug resistance, side effects, and low remission rates. A major obstacle to successful immunotherapy is tumor-evolved mechanisms that inhibit immune (T cell) activity in the tumor microenvironment. To bridge the gap between T cell efficacy in combating lymphoma growth and current drug resistance, we propose to explore a novel metabolic checkpoint of T cell activation in the lymphoma microenvironment. This is the metabolism of the essential branched-chain amino acids (BCAAs) driven by the cytosolic and mitochondrial branched-chain aminotransferases (BCATc and BCATm, respectively).

By creating unique transgenic animal models of BCATc and BCATm, our laboratory aims to uncover the potential of the BCAA metabolic pathway as a new paradigm in the T cell-driven anti-lymphoma immunity. A combination of animal models, molecular, biochemical, bioinformatic, and metabolic approaches will be utilized to achieve the goals of this project.